Our aim is to understand the structure-function relationship of modified nucleosides and nucleotides in nucleic acids. Our objective is to establish by x-ray diffraction techniques the three dimensional structures of mRNA caps, oligo 2-5's that are the signal of dsRNA in interferon treated cells and of short pieces of oligonucleotides with and without mutagens and carcinogens intercalated or covalently bound. The stereochemistry of 2'-5' and 5'-5' phosphodiester links will be studied and will be compared with the stereochemistry of 3'-5' links. Our aim is to understand why 3'-5' phosphodiester bonds and not the 2'-5' phosphodiester bonds are actually used in all genetic information transfer though the 2'-5' links are formed more readily. The conformational flexibility of 5'-5' links will be explored using our structural studies on NAD (nicotinamide adenine dinucleotide) and its several derivatives like NADH, NADP, NADPH and their analogs. Oligonucleotides of varying lengths and sequences are being synthesized and studied using x-ray diffraction. Stereochemical studies on oligonucleotides modified with carcinogens and of cis-synphotodimer of thymidylyl (3'-5')thymidine are in progress.